2013 Grants - Bredesen

An Exploratory Safety, PK/PD, and Preliminary Efficacy Study of F03 in MCI

2013 Part the Cloud Translational Research Bridge Funding for Alzheimer's Disease in Northern California

Beta-amyloid is a protein fragment implicated in nerve cell toxicity and formation of amyloid plaques in Alzheimer's disease. Beta-amyloid is produced from its parent molecule, amyloid precursor protein (APP), by the action of several cell proteins or molecular scissors. Previous clinical trials in people with Alzheimer's disease have studied drugs to block the proteins that cut APP, but those trials have found the drugs to have limited effectiveness or safety concerns.

Researchers working at the Buck Institute for Research on Aging have identified a new drug candidate that works by a different mechanism and has shown promise in early studies in animals. This drug, F03, binds to APP instead of the proteins that cuts APP. By doing so, F03 alters how APP is processed, leading to the formation of less toxic forms of beta-amyloid. In animal models of Alzheimer's disease, F03 reduced biomarkers of Alzheimer's disease and improved measures of short-term and long-term memory. Furthermore, the drug could be administered by mouth and was able to penetrate into the brain.

The Buck Institute researchers, represented by lead scientist Dale E. Bredesen, M.D., have proposed a first-step clinical trial of F03 in humans. This trial, known as a phase Ib/2a trial, will enroll 36 people who have amnestic mild cognitive impairment (aMCI), a condition characterized by declining memory function that sometimes precedes Alzheimer's disease. The researchers plan to administer F03 to these volunteers and study how it is absorbed and processed by the body and what effects it has on the brain and other body systems. Brain changes will be monitored using brain imaging and tests of brain function. This study will help determine what dose of F03 should be used regarding its safety, and if the drug shows preliminary signs of efficacy warranting further study in phase II or phase III trials, further understanding the effectiveness and safety.

These studies could also provide clues about the fundamental causes of Alzheimer's disease and the role of different forms of beta-amyloid. This information could be used in the future to design even better treatment strategies for preventing or halting disease progression.